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| ID | Type | Description | Link |
|---|---|---|---|
| AL-034-1201 | Other Identifier | Alios BioPharma Inc. |
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This is a Phase 1 first-in-human (FIH) study evaluating single and multiple dose administration of AL-034 in healthy adult participants. The aim is to examine the safety (including pharmacodynamic [PD] biomarker assessments), tolerability, and pharmacokinetics (PK) of increasing single ascending doses (SADs) (Part 1) and multiple ascending doses (MADs) (Part 2) of AL-034. The potential food effect will be investigated in healthy adult participants at one or optionally 2 single dose level(s).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1: Single Ascending Dose (SAD) | Experimental | Participants will receive single oral dose of AL-034 (oral solution) (the starting dose in Cohort 1 of Part 1 will be 0.2 milligram [mg]) or matching placebo under fasted condition (Cohorts 1 to 5 or optional Cohort 7) on Day 1. Participants may receive AL-034 in a fed state (Cohort 6) to evaluate the effect of food on the pharmacokinetics (PK) of AL-034. |
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| Part 2: Multiple-Dose Administration (MAD) | Experimental | Participants will receive multiple oral doses of AL-034 or matching placebo for 4 consecutive weeks either once weekly (Qwk - for 4 doses) or every two weeks (Q2wk - for 3 doses) under fed or fasted conditions. The starting dose for Part 2 will be determined based on the initial PK and safety/tolerability data from Part 1. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AL-034 | Drug | Participants will receive single oral dose of AL-034 under fed or fasted conditions in part 1 and part 2 |
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| Measure | Description | Time Frame |
|---|---|---|
| Part 1: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability | An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. | Approximately up to 9 weeks |
| Part 2: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability | An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. | Approximately up to 12 weeks |
| Part 1: Number of Participants With AEs by Severity | Severity of AEs will be graded according to the Division of Acquired Immune Deficiency Syndrome (DAIDS) Toxicity Grading Scale as follows: Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe); Grade 4 (potentially life-threatening); and Grade 5 (death related to the AE). | Approximately up to 9 weeks |
| Part 2: Number of Participants With AEs by Severity | Severity of AEs will be graded according to the Division of AIDS (DAIDS) Toxicity Grading Scale as follows: Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe); Grade 4 (potentially life-threatening); and Grade 5 (death related to the AE). | Approximately up to 12 weeks |
| Part 1: Number of Participants with Clinically Significant Changes in Physical Examination | Number of participants with clinically significant changes in the physical examination (including height, body weight measurement, and skin examination) will be reported. | Approximately up to 9 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Part 1: Maximum Observed Plasma Concentration (Cmax) of AL-034 Following Single Dose Administration in Fed State | The Cmax is the maximum observed concentration of AL-034 in plasma following SAD administration. | Day 1: predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose |
| Part 2: Area Under the Plasma Concentration Time Curve (AUC) of AL-034 Following Single Dose Administration in Fed State |
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INCLUSION CRITERIA Each potential participant must satisfy all of the following criteria to be enrolled in the study
EXCLUSION CRITERIA Any potential participant who meets any of the following criteria will be excluded from participating in the study
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| Name | Affiliation | Role |
|---|---|---|
| Alios Biopharma Inc. Clinical Trial | Alios Biopharma Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Auckland Clinical Studies, Ltd. | Auckland | New Zealand |
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| ID | Term |
|---|---|
| D006509 | Hepatitis B |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D018347 | Hepadnaviridae Infections |
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Dose Escalation
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| Placebo | Drug | Participants will receive single oral dose of matching placebo (oral solution) under fed or fasted conditions in part 1 and part 2. |
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| Part 2: Number of Participants with Clinically Significant Changes in Physical Examination | Number of participants with clinically significant changes in the physical examination (including height, body weight measurement, and skin examination) will be reported. | Approximately up to 12 weeks |
| Part 1: Number of Participants with Vital Sign Abnormalities | Number of participants with vital signs abnormalities (vital signs includes body temperature, pulse rate, respiratory rate, oxygen saturation [SaO2] and blood pressure) will be reported. | Approximately up to 9 weeks |
| Part 2: Number of Participants with Vital Sign Abnormalities | Number of participants with vital signs abnormalities (vital signs includes body temperature, pulse rate, respiratory rate, oxygen saturation [SaO2] and blood pressure) will be reported. | Approximately up to 12 weeks |
| Part 1: Number of Participants with Laboratory Abnormalities | Number of participants with clinical laboratory abnormalities (serum chemistry, hematology, and coagulation) will be reported. | Approximately up to 9 weeks |
| Part 2: Number of Participants with Laboratory Abnormalities | Number of participants with clinical laboratory abnormalities (serum chemistry, hematology, and coagulation) will be reported. | Approximately up to 12 weeks |
| Part 1: Number of Participants with Holter Monitoring Abnormalities | Number of participants with Holter monitoring abnormalities (related to heart's activity such as rate and rhythm) will be reported. | Approximately up to 9 weeks |
| Part 2: Number of Participants with Holter Monitoring Abnormalities | Number of participants with Holter monitoring abnormalities (related to heart's activity such as rate and rhythm) will be reported. | Approximately up to 12 weeks |
| Part 1: Number of Participants with Electrocardiogram (ECG) Abnormalities | Number of participants with electrocardiogram (ECG) abnormalities will be reported. | Approximately up to 9 weeks |
| Part 2: Number of Participants with Electrocardiogram (ECG) Abnormalities | Number of participants with electrocardiogram (ECG) abnormalities will be reported. | Approximately up to 12 weeks |
| Part 1: Number of Participants with Cytokine Release Syndrome (CRS) | Number of participants with CRS will be reported. CRS is defined as a disorder characterized by nausea, headache, tachycardia, hypotension, rash, and/or shortness of breath. | Approximately up to 9 weeks |
| Part 2: Number of Participants with Cytokine Release Syndrome (CRS) | Number of participants with CRS will be reported. CRS is defined as a disorder characterized by nausea, headache, tachycardia, hypotension, rash, and/or shortness of breath. | Approximately up to 12 weeks |
| Part 1: Number of Participants with Cytokine Release Syndrome (CRS) by Severity | Severity of CRS will be graded according to DAIDS as follows: Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe); and Grade 4 (potentially life-threatening). | Approximately up to 9 weeks |
| Part 2: Number of Participants with Cytokine Release Syndrome (CRS) by Severity | Severity of CRS will be graded according to DAIDS as follows: Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe); and Grade 4 (potentially life-threatening). | Approximately up to 12 weeks |
| Part 1: Maximum Observed Plasma Concentration (Cmax) of AL-034 Following Single Dose Administration in Fasted State | The Cmax is the maximum observed concentration of AL-034 in plasma following single ascending dose (SAD) administration. | Day 1: predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose |
| Part 2: Maximum Observed Plasma Concentration (Cmax) of AL-034 Following Repeated Dose Administration | The Cmax is the maximum observed concentration of AL-034 in plasma following multiple ascending dose (MAD) administration. | Days 1, 22, and 29: predose, and 0.5, 1, 2, and 12 hours postdose |
| Part 1: Area Under the Plasma Concentration Time Curve (AUC) of AL-034 Following Single Dose Administration in Fasted State | AUC is the area under the plasma concentration time curve of AL-034 in plasma following SAD administration. | Day 1: predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose |
| Part 2: Area Under the Plasma Concentration Time Curve (AUC) of AL-034 Following Repeated Dose Administration | AUC is the area under the plasma concentration time curve of AL-034 in plasma following MAD administration. | Days 1, 22, and 29: predose, and 0.5, 1, 2, and 12 hours postdose |
| Part 1: AL-034 Concentration in Urine Following a Single Dose Administration | Concentration in urine of AL-034 following a single dose administration will be determined. | Day 1: 0 to 6, 6 to 12, and 12 to 24 hours postdose |
| Part 2: AL-034 Concentration in Urine Following Repeated Dose Administration | Concentration in urine of AL-034 following MAD administration will be determined. | Day 1: 0 to 6, 6 to 12, and 12 to 24 hours postdose |
AUC is the area under the plasma concentration time curve of AL-034 in plasma following SAD administration. |
| Day 1: predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose |
| Background |
| Chang TT, Gish RG, de Man R, Gadano A, Sollano J, Chao YC, Lok AS, Han KH, Goodman Z, Zhu J, Cross A, DeHertogh D, Wilber R, Colonno R, Apelian D; BEHoLD AI463022 Study Group. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. N Engl J Med. 2006 Mar 9;354(10):1001-10. doi: 10.1056/NEJMoa051285. |
| 21143343 | Background | Cohen C, Holmberg SD, McMahon BJ, Block JM, Brosgart CL, Gish RG, London WT, Block TM. Is chronic hepatitis B being undertreated in the United States? J Viral Hepat. 2011 Jun;18(6):377-83. doi: 10.1111/j.1365-2893.2010.01401.x. Epub 2010 Dec 8. |
| 22436845 | Background | European Association For The Study Of The Liver. EASL clinical practice guidelines: Management of chronic hepatitis B virus infection. J Hepatol. 2012 Jul;57(1):167-85. doi: 10.1016/j.jhep.2012.02.010. Epub 2012 Mar 20. No abstract available. |
| Background | Fridericia LS. Die Systolendauer im Elektrokardiogramm bei normalen Menschen und bei Herzkranken. Acta Med Scand 1920; 53: 469-486 |
| Background | Investigator's Brochure: JNJ 64794964 (AL-034). Edition 1. Janssen Research & Development (May 2017). |
| 16525138 | Background | Lai CL, Shouval D, Lok AS, Chang TT, Cheinquer H, Goodman Z, DeHertogh D, Wilber R, Zink RC, Cross A, Colonno R, Fernandes L; BEHoLD AI463027 Study Group. Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B. N Engl J Med. 2006 Mar 9;354(10):1011-20. doi: 10.1056/NEJMoa051287. |
| 19399811 | Background | Liang TJ. Hepatitis B: the virus and disease. Hepatology. 2009 May;49(5 Suppl):S13-21. doi: 10.1002/hep.22881. |
| 26566246 | Background | Lok AS, McMahon BJ, Brown RS Jr, Wong JB, Ahmed AT, Farah W, Almasri J, Alahdab F, Benkhadra K, Mouchli MA, Singh S, Mohamed EA, Abu Dabrh AM, Prokop LJ, Wang Z, Murad MH, Mohammed K. Antiviral therapy for chronic hepatitis B viral infection in adults: A systematic review and meta-analysis. Hepatology. 2016 Jan;63(1):284-306. doi: 10.1002/hep.28280. Epub 2015 Nov 13. |
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| 15371578 | Background | Marcellin P, Lau GK, Bonino F, Farci P, Hadziyannis S, Jin R, Lu ZM, Piratvisuth T, Germanidis G, Yurdaydin C, Diago M, Gurel S, Lai MY, Button P, Pluck N; Peginterferon Alfa-2a HBeAg-Negative Chronic Hepatitis B Study Group. Peginterferon alfa-2a alone, lamivudine alone, and the two in combination in patients with HBeAg-negative chronic hepatitis B. N Engl J Med. 2004 Sep 16;351(12):1206-17. doi: 10.1056/NEJMoa040431. |
| 26019743 | Background | Phyo WW, Soh AY, Lim SG, Lee GH. Search for a cure for chronic hepatitis B infection: How close are we? World J Hepatol. 2015 May 28;7(9):1272-81. doi: 10.4254/wjh.v7.i9.1272. |
| 15615823 | Background | Poggio ED, Wang X, Greene T, Van Lente F, Hall PM. Performance of the modification of diet in renal disease and Cockcroft-Gault equations in the estimation of GFR in health and in chronic kidney disease. J Am Soc Nephrol. 2005 Feb;16(2):459-66. doi: 10.1681/ASN.2004060447. Epub 2004 Dec 22. |
| 26231459 | Background | Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott JJ. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet. 2015 Oct 17;386(10003):1546-55. doi: 10.1016/S0140-6736(15)61412-X. Epub 2015 Jul 28. |
| 8363190 | Background | Williamson DF. Descriptive epidemiology of body weight and weight change in U.S. adults. Ann Intern Med. 1993 Oct 1;119(7 Pt 2):646-9. doi: 10.7326/0003-4819-119-7_part_2-199310011-00004. |
| Background | World Health Organization (WHO). Hepatitis B Fact Sheet. Available at: http://www.who.int/mediacentre/factsheets/fs204/en/. Accessed 31 January 2017 |
| D004266 |
| DNA Virus Infections |
| D014777 | Virus Diseases |
| D006525 | Hepatitis, Viral, Human |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |